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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to evaluate the lipid-lowering effect of simvastatin in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolaemia while possible clinical and biochemical adverse effects were monitored for. Forty-three NIDDM patients with hypercholesterolaemia (total cholesterol > 6.5 mmol/l) used simvastatin after a detailed clinical laboratory evaluation as well as a 4-week wash-out period and a 4-week placebo baseline period. Simvastatin treatment was initiated with a 10 mg dose for 6 weeks; this was increased to 20 mg and 40 mg at 12 and 18 weeks of follow-up respectively if the total cholesterol level had not decreased to below 5.17 mmol/l. Patients were placed on a lipid-lowering diet and continued to take any regular non-lipid-lowering medication throughout the trial; side-effects were monitored at 6-week intervals until patients had taken simvastatin for 24 weeks. The mean total cholesterol level was reduced by 22.2% at the first follow-up visit, and by 24.2%, 23.3%, and 28.5% at the second, third and fourth follow-up visits respectively compared with base-line levels. A dose of 10 mg simvastatin brought about a reduction in total cholesterol similar to those found with higher doses. The mean triglyceride level was reduced by 20.9% with 20 mg simvastatin. The high-density lipoprotein cholesterol level was not altered significantly and neither was the control of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Simvastatin in non-insulin-dependent diabetic patients with hypercholesterolaemia. 146 88

The Authors examine the relationship between diabetes mellitus, lipid metabolism and atherosclerosis with particular emphasis on the role of insulin and on the therapeutic consequences. The results of a study on the efficacy and tolerability of simvastatin in the treatment of hypercholesterolemia in non insulin-dependent diabetic patients are reported. Simvastatin administration induce a significant reduction and increase in total and HDL cholesterol levels respectively contributes to the decrease of triglycerides without interfering with the metabolic control of diabetic condition.
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PMID:[Diabetes mellitus, hypercholesterolemia, and therapeutic prospects with simvastatin. General considerations and personal contribution]. 149 62

In 10 hypercholesterolemic patients with Type I (insulin-dependent) diabetes, simvastatin 10-40 mg/day was compared to placebo in a randomized, double-blind, cross-over study with treatment periods of 12 weeks. Between each treatment there was a wash-out period of 4 weeks. Compared to placebo, simvastatin reduced total cholesterol by 19% (p less than 0.001) and low density lipoprotein (LDL) cholesterol by 24% (p less than 0.001). Simvastatin therapy reduced plasma triglyceride by 8% and increased high density lipoprotein (HDL) cholesterol by 8%, but neither of these alterations was significant (p greater than 0.05). Diabetic control and daily requirement of insulin were not influenced by simvastatin. In six patients, all men, there were no alterations in the concentrations of dehydroepiandrosterone-sulphate, testosterone, estradiol, prolactin, luteinizing hormone or follicle-stimulating hormone, while sex hormone-binding globulin was significantly (19% (p less than 0.05)) reduced during therapy with simvastatin. Thus, in Type I (insulin-dependent) diabetic patients, simvastatin causes significant reductions in plasma total cholesterol and LDL cholesterol which are similar in magnitude to those observed in non-diabetics. This favourable effect can be obtained without any concomitant negative influence on glucose regulation or total gonadal steroid hormone concentrations.
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PMID:Effect of simvastatin in patients with type I (insulin-dependent) diabetes mellitus and hypercholesterolemia. 157 50

The lipid profiles of 192 patients with functioning renal transplants and their etiologic associations and response to therapy, in particular simvastatin, were assessed. Hypercholesterolemia was present in 71.3% of patients within 3 years following transplantation. There were independent associations of serum cholesterol with prednisone dosage (p < 0.05), renal function (p < 0.05), and smoking (p < 0.05) in the early posttransplant period (up to 3 months posttransplant). Those patients whose immunosuppression included cyclosporin had lower serum cholesterol levels than those receiving azathioprine and prednisone (p < 0.02). Plasma triglyceride levels reflected a marked interindividual variation, and no independent correlations were observed. The presence of diabetes mellitus, hypertension (or the use of antihypertensive agents), or the form or duration of prior dialysis did not independently influence the lipid profiles. During the study period 22 patients died, 54.5% due to vascular causes. Those who died of vascular causes had higher serum cholesterol levels than those who died of other causes, which reached statistical significance at 3 years posttransplant (7.74 +/- 0.4 versus 5.5 +/- 0.52 mmol/L; p < 0.02). Cholestyramine was introduced in 30 patients, only 2 of whom continued with therapy beyond 3 months. Simvastatin was used in 43 patients, 20 of whom were receiving cyclosporin, resulting in a mean reduction in serum cholesterol of 16.5% (p < 0.001) and in serum triglycerides of 21% (p < 0.05). No clinical or biochemical evidence of muscle, liver, or renal toxicity occurred in 15.4 +/- 0.9 months of follow-up.
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PMID:Hyperlipidemia in renal transplant recipients: natural history and response to treatment. 804 Dec 44

Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at high risk of cardiovascular disease for many reasons and especially due to the fact that dyslipidemias are more frequent in this group of patients. Fibrate derivatives are the drugs of choice when hypertriglyceridemia is the main lipid anomaly. When hypercholesterolemia is predominant, the use of resins and nicotinic acid has been advocated but these drugs are poorly tolerated on a long-term basis. We assessed the effect of simvastatin, a recent HMG-CoA reductase inhibitor in 12 NIDDM patients with hypercholesterolemia. After 4 weeks of placebo, which did not significantly modify the lipid values, patients were given simvastatin at increasing dosages (from 10 to a maximum of 40 mg daily) during 24 weeks. Compliance and clinical tolerance were excellent. There was no major biological side effect, but a significant deterioration of glucose control was noted at the end of the study. Simvastatin reduced total cholesterol by 28%, LDL-cholesterol by 36% and apo B by 31%. Concomitantly, there was an increase of HDL-cholesterol by 15%. This improvement of lipid profile persisted during the 24 weeks of treatment. Comparing the patients with pure hypercholesterolemia to those presenting combined hyperlipidemia, it was evident that the hypolipidemic effect was more marked in the diabetic subjects with combined hyperlipidemia.
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PMID:Efficacy of simvastatin for lowering cholesterol in non-insulin dependent diabetic patients with hypercholesterolemia. 806 75

The incidence of atherosclerotic vascular disease is greatly increased in patients with non-insulin-dependent diabetes (NIDDM). The most frequent lipoprotein abnormalities in this type of diabetes are an increase in triglyceride-rich lipoproteins and a decrease in high-density lipoproteins. Hypertriglyceridaemia appears to be a stronger coronary heart disease risk factor in patients with NIDDM than in nondiabetic subjects. Plasma total and low-density lipoprotein cholesterol levels in NIDDM patients and nondiabetic subjects do not differ. Hypercholesterolaemia is, however, as powerful a predictor of coronary heart disease risk in diabetic patients as in nondiabetic subjects. In spite of this knowledge, there is to date no solid evidence to indicate whether correction of dyslipoproteinaemia in order to reduce coronary heart disease risk in patients with NIDDM is more, equally, or less beneficial than it is in nondiabetic subjects. The only available data come from post-hoc subgroup analyses of the Helsinki Heart Study and the Scandinavian Simvastatin Survival Study (4S). Other trials including patients with diabetes are in progress. Only one intervention trial (currently in its treatment phase), the Diabetes Atherosclerosis Intervention Study (DAIS), is specifically designed to examine the lipid hypothesis in patients with NIDDM.
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PMID:Will correction of dyslipoproteinaemia reduce coronary heart disease risk in patients with non-insulin-dependent diabetes? Need for trial evidence. 886 91

Lipid and lipoprotein abnormalities in non-insulin-dependent diabetes mellitus (NIDDM) include particularly elevated levels of total and very-low-density lipoprotein (VLDL) triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate. The worsening of glycemic control deteriorates lipid and lipoprotein abnormalities and particularly total and LDL cholesterol levels are often elevated in patients with poor glycemic control. According to prospective population-based studies total cholesterol is a powerful risk factor for coronary heart disease (CHD) in NIDDM patients as in nondiabetic subjects. In contrast, high total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in NIDDM patients than in nondiabetic individuals, but more prospective studies are needed to substantiate this view. Compositional changes in LDL and VLDL particles may further increase the risk for CHD but epidemiologic data are missing to support this notion. Preliminary data from the Scandinavian Simvastatin Survival Study including 202 diabetic patients seem to indicate that diabetic patients benefit from simvastatin treatment equally to nondiabetic subjects.
J Diabetes Complications
PMID:Dyslipidemia, morbidity, and mortality in non-insulin-dependent diabetes mellitus. Lipoproteins and coronary heart disease in non-insulin-dependent diabetes mellitus. 910

Although hyperlipidemia is a known risk factor for coronary artery disease, lipid-lowering agents were not used widely until recently because evidence was lacking that they could prolong life. In 1987, a large clinical trial, the Scandinavian Simvastatin Survival Study (4S), was designed to test whether such therapy could decrease all-cause mortality in patients with documented coronary artery disease. The prospective, randomized, multicenter trial included 4,444 patients who had had angina pectoris or myocardial infarction (MI), serum total cholesterol of 213-310 mg/dL, and serum triglycerides < or =221 mg/dL. Patients received either simvastatin 20-40 mg/day or placebo and were followed for a median of 5.4 years. Therapy decreased total cholesterol an average of 25%; low-density lipoprotein (LDL) cholesterol, 35%; and triglyceride levels, 10%. Therapy increased high-density lipoprotein (HDL) cholesterol levels 8%. Although noncardiac death rates were similar among the groups, the relative risk of mortality (from any cause) was decreased 30%, and the relative risk of coronary mortality was decreased 42% in the simvastatin arm. The mortality risk reductions were profound in patients > or =60 years of age. Treatment also significantly decreased the relative risk of coronary events and the need for bypass surgery or coronary angioplasty. Patients with diabetes also benefited significantly from simvastatin therapy. The reductions in relative risk of major coronary events were achieved irrespective of such baseline risk factors as hypertension and smoking and such medication factors as aspirin, beta-blocker, and calcium-antagonist use. Simvastatin therapy has been shown to be cost-effective, decreasing per-patient hospitalization costs by 31% or $3,872 in 1995 dollars.
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PMID:Coronary artery disease: the Scandinavian Simvastatin Survival Study experience. 986 Mar 76

Usual risk factors for coronary artery disease account for only 25-50% of increased atherosclerotic risk in diabetes mellitus. Other obvious risk factors are hyperglycemia and dyslipidemia. However, hyperglycemia is a very late stage in the sequence of events from insulin resistance to frank diabetes, whereas lipoprotein abnormalities are manifested during the largely asymptomatic diabetic prodrome and contribute substantially to the increased risk of macrovascular disease. The insulin-resistant diabetes course affects virtually all lipids and lipoproteins. Chylomicron and very-low-density lipoprotein (VLDL) remnants accumulate, and triglycerides enrich high-density lipoprotein (HDL) and low-density lipoprotein (LDL), leading to high levels of potentially atherogenic particles and low levels of HDL cholesterol. Hyperglycemia eventually impairs removal of triglyceride-rich lipoproteins, the accumulation of which accentuates hypertriglyceridemia. As triglycerides increase-still within the so-called normal range-abnormalities in HDL and LDL became more apparent. Thus, when triglycerides are >200 mg/dL, LDL particles are small and dense (when they are <90 mg/dL, the particles are of the large, buoyant variety). The atherogenicity of small, dense LDL particles is attributed to their increased susceptibility to oxidation, but in many patients they may be a marker for insulin resistance or the presence of atherogenic VLDL. Hypertriglyceridemia is associated with atherosclerosis because (1) it is a marker for insulin resistance and atherogenic metabolic abnormalities; and (2) the small size of triglyceride-enriched lipoproteins enables them to infiltrate the blood vessel wall where they are oxidized, bind to receptors on macrophages, and ingested, leading to the development of the atherosclerotic lesion. Various studies (primary prevention with gemfibrozil: Helsinki Heart Study; secondary prevention with simvastatin and pravastatin: Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events [CARE], respectively) have demonstrated that lipid-lowering therapy in type 2 diabetes is effective in decreasing the number of cardiac events. Risk reduction was 22% to 50% (statins) and approximately 65% (fibrate) relative to placebo. It was also noted (in 4S and CARE) that the risk of major coronary events in untreated diabetic patients was 1.5-1.7-fold greater than in untreated nondiabetic patients. Although gemfibrozil (fibric acid derivative) is more effective in decreasing triglycerides and increasing HDL cholesterol in diabetic patients than the statins, it does not change and may even increase LDL-cholesterol levels (fenofibrate may be an exception, decreasing LDL cholesterol by 20-25% in some studies). However, gemfibrozil does increase LDL particle size. Nevertheless, the statins are the current lipid-lowering drugs of choice because the change in LDL-cholesterol-to-HDL-cholesterol ratio is better than with gemfibrozil. Moreover, the diabetic patient may be more likely to benefit from statin therapy than the nondiabetic patient. It should be noted that, in theory, nicotinic acid can correct or improve all lipid or lipoprotein abnormalities in patients with type 2 diabetes. Unfortunately, it is relatively contraindicated because it causes insulin resistance and may precipitate or aggravate hyperglycemia (in addition to its other well-known side effects such as flushing, gastric irritation, development of hepatotoxicity, and hyperuricemia). It is unknown at present whether newer formulations such as once-daily Niaspan may be better tolerated in diabetes. In any case, most patients with type 2 diabetes have risk factors for coronary artery disease and qualify for aggressive LDL cholesterol-lowering therapy. At the same time, it is presently unknown whether improved glycemic control decreases coronary artery disease risk in such patients.
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PMID:Diabetic dyslipidemia. 991 65

Atheroma is related to low-density lipoprotein (LDL) composition. LDL in diabetic patients-a group with increased risk of severe atheroma-has been shown by our group and others to have various compositional alterations that are potentially atherogenic. Little is known about the relationship between LDL turnover and composition. This study examined the relationship between LDL composition and turnover in non-insulin-dependent diabetes mellitus (NIDDM) patients. Twenty-two NIDDM patients with a mean plasma cholesterol of 6.6+/-1.5 mmol/L were studied. Twelve subjects were hypercholesterolemic (mean cholesterol, 7.7+/-0.8 mmol/L), and eight of these agreed to be studied a second time after 4 weeks of treatment with simvastatin. LDL was isolated by density gradient ultracentrifugation, iodinated, and reinjected into the patient. LDL turnover was determined by measuring the clearance of [125I]-LDL from plasma over a 10-day period. The LDL residence time, determined using a biexponential model, correlated negatively with the body mass index (BMI) (r = -.73, P<.001) and serum triglycerides (r = - .57, P<.01). There was a significant inverse correlation between LDL residence time and the LDL esterified to free cholesterol ratio in hypercholesterolemic subjects (r = -.94, P<.001). There was a significant inverse relationship between LDL residence time and both hemoglobin A1c (HbA1c) and fasting blood glucose in these subjects before treatment (P<.005). After simvastatin therapy, the relationships were no longer significant. Simvastatin treatment was associated with a shorter LDL residence time (P<.01) and a decrease in LDL glycation (P<.001) with virtually no change in diabetic control (HbA1c, 6.0%+/-3.1% v. 6.3%+/-3.3%, NS). This study suggests that a decrease in residence time by upregulation of the LDL receptor with simvastatin alters LDL composition in a way that is likely to render the particle less atherogenic.
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PMID:Association between low-density lipoprotein composition and its metabolism in non-insulin-dependent diabetes mellitus. 992 Jan 55


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